Table 1
Comparative Framework: ESC/EAS 2025 vs ACC/AHA 2026 vs LAI 2023 vs ILEP 2024/2025.
| DOMAIN | ESC/EAS 2025 | ACC/AHA 2026 | LAI (INDIA) 2023 | ILEP (2024/2025) | CLINICAL INTERPRETATION |
|---|---|---|---|---|---|
| Underlying Philosophy | Target-driven, risk-tiered LDL lowering | Personalized risk estimation with a goal-based hybrid model | Early aggressive approach reflecting high baseline risk | ‘Earlier, lower, longer’ + upfront intensive therapy | Unified causal paradigm of LDL exposure across the lifespan |
| Risk Assessment Tool | SCORE2/SCORE2-OP | PREVENT (10- & 30-year risk) | LAI ASCVD Risk Calculator | Risk-based + emphasis on clinical risk dominance over scores in high-risk states | Different tools, shared goal: lifetime risk identification |
| Risk Categories | Five tiers: Low → Extreme | Four tiers: Borderline → Very High | Five tiers incl. Extreme (A/B/C subclassification) | Expanded very high & extreme risk definitions | Variation reflects epidemiology, not disagreement |
| Definition of Very High Risk | ASCVD, CKD, DM with TOD, SCORE2 ≥20% | ≥2 ASCVD events OR one event + high-risk features | ASCVD, DM with complications, HeFH | ASCVD + high residual risk; includes post-ACS/stroke emphasis | Broad alignment across frameworks |
| Extreme Risk Category | Recurrent ASCVD or polyvascular disease | Not formally defined | Strongly emphasized; subclassified (A/B/C) | Strongly emphasized; includes ACS, stroke, polyvascular disease, FH | Consolidates ultra-high-risk phenotype |
| LDL-C Targets (Very High Risk) | <55 mg/dL + ≥50% reduction | <55–70 mg/dL + individualized | <50 mg/dL | <55 mg/dL with rapid attainment via combination therapy | Converging targets with differing urgency |
| LDL-C Targets (Extreme Risk) | <40 mg/dL | Not defined | <50 mg/dL; optional <30 mg/dL (A/B); up to 10–15 mg/dl in Category C | <40 mg/dL; consider <30 mg/dL in selected patients | Emergence of ultra-low LDL paradigm |
| Role of CAC | Risk modifier | Direct determinant of therapy | Risk-enhancing feature | Secondary to immediate treatment in high-risk states | CAC shifting from refinement → trigger |
| CAC-Based Targets | Not target-defining | CAC-guided LDL thresholds | CAC-driven intensification | Less emphasized vs clinical risk urgency | Imaging complements—not replaces—clinical risk |
| Imaging Beyond CAC | Limited | Increasing (CT-based) | Strong (carotid/femoral plaque) | Adjunctive; not delaying therapy | Imaging is evolving, but not central in acute risk |
| Non-HDL-C Role | Secondary target | Co-primary target | Co-primary target | Co-equal to LDL-C in high TG/metabolic states | Reflects total atherogenic burden |
| ApoB Role | Recommended in discordance | Refines risk | Integrated in high-risk | Preferred marker of atherogenic particle burden | ApoB gaining primacy |
| Lp(a) | Risk enhancer | Universal one-time measurement | Strong emphasis | Central residual risk factor; strong emphasis | Universal agreement on causal role |
| Therapeutic Strategy | Stepwise escalation | Flexible sequencing | Early combination therapy | Upfront combination therapy (double/triple) in high-risk | Shift from escalation → early intensification |
| Primary Prevention | Structured, risk-based | Earlier intervention (≥3–5% risk) | Lower thresholds | Early intervention guided by lifetime exposure | Movement toward earlier treatment |
| Secondary Prevention (ACS/Stroke) | Early statin + ezetimibe | Flexible early intensification | Immediate aggressive combination | Immediate upfront combination therapy mandatory | ‘Treat fast, treat deep’ paradigm |
| Severe Hypercholesterolemia (LDL ≥190) | High intensity + add-ons | Early add-on therapy | Aggressive multi-drug | Immediate combination ± PCSK9/Inclisiran | No delay strategy across frameworks |
| Triglyceride Approach | Secondary focus | Integrated | Strong emphasis | Residual risk focus (TRLs, remnant cholesterol) | TG-rich lipoproteins increasingly relevant |
| Residual Risk Concept | Expanding beyond LDL | ApoB, Lp(a), inflammation | Strong metabolic focus | Multidimensional (ApoB, Lp(a), TG, inflammation) | Shift to a multi-marker paradigm |
| Time-to-Target Philosophy | Stepwise, structured | Flexible | Early aggressive | Immediate goal attainment (weeks, not months) | Same endpoint, different speed |
| Population Context | Aging European cohorts | Heterogeneous population | Premature ASCVD in South Asians | Global, high-risk focus (ACS/stroke/FH) | Epidemiology shapes strategy |
| Implementation Style | Algorithmic, system-driven | Shared decision-making | Prevention-oriented | Outcome-driven, intensity-focused | Differences reflect systems, not science |
[i] Abbreviations: ACC/AHA = American College of Cardiology/American Heart Association; ACS = acute coronary syndrome; ASCVD = atherosclerotic cardiovascular disease; ApoB = apolipoprotein B; CAC = coronary artery calcium; CKD = chronic kidney disease; CT = computed tomography; DM = diabetes mellitus; EAS = European Atherosclerosis Society; ESC = European Society of Cardiology; FH = familial hypercholesterolemia; HeFH = heterozygous familial hypercholesterolemia; HDL-C = high-density lipoprotein cholesterol; ILEP = International Lipid Expert Panel; LAI = Lipid Association of India; LDL-C = low-density lipoprotein cholesterol; Lp(a) = lipoprotein(a); TG = triglycerides; TRLs = triglyceride-rich lipoproteins.